Regulation of the calcium channel α1G subunit by divalent cations and organic blockers

The pharmacological properties of the expressed murine T-type or alpha(1G) channel were characterized using the whole cell patch clamp configuration. Ba2+ or Ca2+ were used as charge carriers. Both I-Ba and I-Ca were blocked by Ni2+ and Cd2+ with IC50 values of 0.47+/-0.04 and 1.13+/-0.06 mM (Ni2+) and 162+/-13 and 658+/-23 mu M (Cd2+), respectively. Ni2+, but not Cd2+, modified the gating of channel activation. Ni2+ consistently accelerated channel deactivation while Cd2+ had a similar effect only on I-Ca. The alpha(1G) channel was potently blocked by mibefradil in a dose- and voltage-dependent manner. I-Ba was moderately blocked by phenytoin (IC50 73.9+/-1.9 mu M) and was resistant to the block by valproate. Also 3 mM ethosuximide blocked 20 and 35% of the I-Ba at a HP of -100 and -60 mV, respectively, while 5 mM amiloride inhibited I-Ba by 38% and significantly slowed current activation. The alpha(1G) channel was not affected by 10 mu M tetrodotoxin. Both 1 mu M (+)isradipine and 10 mu M nifedipine inhibited 18 and 14% of I-Ba amplitude at a HP of -100 mV, and 23% and 29% of I-Ba amplitude at a HP of -60 mV, respectively. The alpha(1G) current was minimally activated by 1 mu M Bay K 8644. (C) 2000 Elsevier Science Ltd. All rights reserved.